Sound activates not only the cochlea but also the vestibular end organs. Research on this phenomenon led to the discovery of the sound-evoked vestibular myogenic potentials recorded from the sternocleidomastoid muscles (cervical VEMP, or cVEMP). Since the cVEMP offers simplicity and the ability to stimulate each labyrinth separately, its values as a test of human vestibular function are widely recognized. Currently, the cVEMP is interpreted as a test of saccule function based on the assumption that clicks primarily activate the saccule. However, sound activation of vestibular end organs other than the saccule has been reported. To provide the neural basis for interpreting clinical VEMP testing, we employed the broadband clicks used in clinical VEMP testing to examine the sound-evoked responses in a large sample of vestibular afferents in Sprague-Dawley rats. Recordings were made from 924 vestibular afferents from 106 rats: 255 from the anterior canal (AC), 202 from the horizontal canal (HC), 177 from the posterior canal (PC), 207 from the superior vestibular nerve otolith (SO), and 83 from the inferior nerve otolith (IO). Sound sensitivity of each afferent was quantified by computing the cumulative probability of evoking a spike (CPE). We found that clicks activated irregular afferents (normalized coefficient of variation of interspike intervals >0.2) from both the otoliths (81%) and the canals (43%). The order of end organ sound sensitivity was SO = IO > AC > HC > PC. Since the sternocleidomastoid motoneurons receive inputs from both the otoliths and the canals, these results provide evidence of a possible contribution from both of them to the click-evoked cVEMP.

Multiplicative computation is a basic operation that is crucial for neural information processing, but examples of multiplication by neural pathways that perform well-defined sensorimotor transformations are scarce. Here in behaving monkeys, we identified a multiplication of vestibular and eye position signals in the vestibulo-ocular reflex (VOR). Monkeys were trained to maintain fixation on visual targets at different horizontal locations and received brief unilateral acoustic clicks (1 ms, rarefaction, 85 approximately 110 db NHL) that were delivered into one of their external ear canals. We found that both the click-evoked horizontal eye movement responses and the click-evoked neuronal responses of the abducens neurons exhibited linear dependencies on horizontal conjugate eye position, indicating that the interaction of vestibular and horizontal conjugate eye position was multiplicative. Latency analysis further indicated that the site of the multiplication was within the direct VOR pathways. Based on these results, we propose a novel neural mechanism that implements the VOR gain modulation by fixation distance and gaze eccentricity. In this mechanism, the vestibular signal from a single labyrinth interacts multiplicatively with the position signals of each eye (Principle of Multiplication). These effects, however, interact additively with the other labyrinth (Principle of Addition). Our analysis suggests that the new mechanism can implement the VOR gain modulation by fixation distance and gaze eccentricity within the direct VOR pathways.

Acoustic activation of the vestibular system has been well documented in humans and animal models. In the past decade, sound-evoked myogenic potentials in the sternocleidomastoid muscle (cVEMP) and the extraocular muscles (oVEMP) have been extensively studied, and their potentials as new tests for vestibular function have been widely recognized. However, the extent to which sound activates the otolith and canal pathways remains controversial. In the present study, we examined this issue in a recently developed nonhuman primate model of acoustic activation of the vestibular system, i.e., sound-evoked vestibuloocular reflexes (VOR) in behaving monkeys. To determine whether the canal and otolith VOR pathways are activated by sound, we analyzed abducens neurons' responses to clicks that were delivered into either ear. The main finding was that clicks evoked short-latency excitatory responses in abducens neurons on both sides. The latencies of the two responses, however, were different. The mean latency of the contralateral and ipsilateral abducens neurons was 2.44±0.4 and 1.65±0.28 ms, respectively. A further analysis of the excitatory latencies, in combination with the known canal and otolith VOR pathways, suggests that the excitatory responses of the contralateral abducens neurons were mediated by the contralateral disynaptic VOR pathways that connect the lateral canal to the contralateral abducens neurons, and the excitatory responses of the ipsilateral abducens neurons were mediated by the ipsilateral monosynaptic VOR pathways that connect the utricle to the ipsilateral abducens neurons. These results provide new insights into the understanding of the neural basis for sound-evoked vestibular responses, which is essential for developing new tests for both canal and otolith functions in humans.

It is well established that the vestibulo-ocular reflex (VOR) depends not only on sensory stimulation but also on the behavioral context associated with the stimulation. Recent modeling studies suggested that including a non-linearity in the activation function of the VOR neurons achieves the desired context-dependence for the VOR without resorting to currently assumed complex cortical computations. With the non-linearity, neurons operate as non-linear summers of incoming activity with sensitivities modulated by their activation levels. In this study we examined whether such a non-linearity exists in the unilateral VOR pathways in behaving monkeys. Acoustic clicks were employed to evoke unilateral VOR responses during fixation, head motion and smooth pursuit. We found that the click-evoked unilateral VOR responses did not simply sum in a linear manner with the eye movements initiated by head or target motion. Instead, the same acoustic click evoked larger eye movements if the ongoing eye movements were in the same direction. We also showed that the interaction between the ongoing eye movement and the click-evoked response was close to being multiplicative. These results revealed a previous unknown non-linearity in the unilateral VOR pathways, which may have important implications on the neural implementation of the context-dependence for the VOR.

Since the frequency tuning for the bone-conducted sound-evoked OVEMP (BOVEMP) was different from that of the air-conducted sound-evoked OVEMP (AOVEMP), we hypothesize that the BOVEMP and AOVEMP are generated by activation of different vestibular end organs.

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It is well known that the vestibulo-ocular reflex (VOR) is conjugate when measured in the dark with minimal vergence. But the neural basis of the VOR conjugacy remains to be identified. In the present study, we measured the VOR conjugacy during single labyrinth stimulation to examine whether the VOR conjugacy depends on reciprocal stimulation of the two labyrinths. There are conflicting views on this issue. First, since the vestibular signals carried by the ascending tract of Deiters' are distributed exclusively to the motoneurons of the ipsilateral eye, the neural innervations after single labyrinth stimulation are not symmetrical for the two eyes. Thus, single labyrinth stimulation may generate disjunctive VOR responses. Second, the only published study on this issue was an electrooculography (EOG) study that reported disjunctive VOR responses during unilateral caloric irrigation (Wolfe in Ann Otol 88:79–85, 1979). Third, the VOR during unilateral caloric stimulation performed in clinical vestibular tests is routinely perceived to be conjugate. To resolve these conflicting views, the present study examined the VOR conjugacy during single labyrinth stimulation by recording binocular eye position signals in awake monkeys with a search coil technique. In contradiction to the previous EOG study and the prediction based on the asymmetry of the unilateral brainstem VOR circuits, we found that the VOR during unilateral caloric irrigation was conjugate over a wide range of conditions. We conclude that the net neural innervations received by the two eyes are symmetrical after single labyrinth stimulation, despite the apparent asymmetry in the unilateral VOR pathways. A novel role for the ascending tract of Deiters' in the VOR conjugacy is proposed.

Vestibular evoked myogenic potentials (VEMP) have been used to assess otolith function in clinics worldwide. However, there are accumulating evidence suggesting that the clinically used sound stimuli activate not only the otolith afferents, but also the canal afferents, indicating canal contributions to the VEMPs. To better understand the neural mechanisms underlying the VEMPs and develop discriminative VEMP protocols, we further examined sound-evoked responses of the vestibular nucleus neurons and the abducens neurons, which have the interneurons and motoneurons of the vestibulo-ocular reflex (VOR) pathways. Air-conducted clicks (50–80 dB SL re ABR threshold, 0.1 ms duration) or tone bursts (60–80 dB SL, 125–4,000 Hz, 8 ms plateau, 1 ms rise/fall) were delivered to the ears of Sprague-Dawley or Long-Evans rats. Among 425 vestibular nucleus neurons recorded in anesthetized rats and 18 abducens neurons recorded in awake rats, sound activated 35.9% of the vestibular neurons that increased discharge rates for ipsilateral head rotation (Type I neuron), 15.7% of the vestibular neurons that increased discharge rates for contralateral head rotation (Type II neuron), 57.2% of the vestibular neurons that did not change discharge rates during head rotation (non-canal neuron), and 38.9% of the abducens neurons. Sound sensitive vestibular nucleus neurons and abducens neurons exhibited characteristic tuning curves that reflected convergence of canal and otolith inputs in the VOR pathways. Tone bursts also evoked well-defined eye movements that increased with tone intensity and duration and exhibited peak frequency of ∼1,500 Hz. For the left eye, tone bursts evoked upward/rightward eye movements for ipsilateral stimulation, and downward/leftward eye movements for contralateral stimulation. These results demonstrate that sound stimulation results in activation of the canal and otolith VOR pathways that can be measured by eye tracking devices to develop discriminative tests of vestibular function in animal models and in humans.